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Nat Genet. 2003 Jan;33(1):25-32. Epub 2002 Dec 2.

Positional identification of Ncf1 as a gene that regulates arthritis severity in rats.

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Section for Medical Inflammation Research and Department of Cell and Molecular Biology, Sölvegatan 19, I11 BMC, Lund University, S-22184 Lund, Sweden.


The identification of genes underlying quantitative-trait loci (QTL) for complex diseases, such as rheumatoid arthritis, is a challenging and difficult task for the human genome project. Through positional cloning of the Pia4 QTL in rats, we found that a naturally occurring polymorphism of Ncf1 (encoding neutrophil cytosolic factor 1, a component of the NADPH oxidase complex) regulates arthritis severity. The disease-related allele of Ncf1 has reduced oxidative burst response and promotes activation of arthritogenic T cells. Pharmacological treatment with substances that activate the NADPH oxidase complex is shown to ameliorate arthritis. Hence, Ncf1 is associated with a new autoimmune mechanism leading to severe destructive arthritis, notably similar to rheumatoid arthritis in humans.

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